Process for the production of quinoline-4-carboxylic acids



Patented July 10, 1928.

UNITED STATES PAT-ENT- OFFICE.

ALFRED HKUSSLER, OF NIEDER-INGELHEIM-ON-THE-RHINE, GERMANY, ASSIGNOR TO.

0. H. BOEHRIN'GER SOHN, CHEMISCHE FABRIK, OF NIEDER-INGELHEIM-ON-THE-RHINEfGERMANY, A FIRM.

PROCESS FOR THE PRODUCTION OF QUINOLINE-l-CARBOXYLIG ACIDS.

No Drawing. Application filed December 8, 1926, Serial No. 153,454, andin Germany February 6, 1926.

It is known to produce Q-phenylquinolinet-carboxylic acid by bringingequal molecules of pyroracemic acid, bcnzaldehyde and aniline intoreaction in alcoholic solution. It is furthermore known to produce firstof all the condensa. ion product of aniline and beuzaldehyde and tointroduce pyroracemic acid gradually into a boiling alcoholic solutionthereof, about 1 molecule of pyroracemic acid being employed per 1 partof the condensation product.

It has now been found that surprising increases of yield, together withother advantages, are achieved by employing more than 1.5 molecules ofthe condensation product (beuzylidene-aniline), For example 1.5 to 2molecules per 1 molecule of pyroracemic acid.

The invention may he carried into practice by, for example, adding 1molecule of pyroracemic acid, by itself or, for example, in alcoholic oraqueous solution, to a hot alcoholic solution of 1.6 to 1.8 molecules ofl.)enzylide ne-aniline and by then subjecting; the reaction-mixture to asubsequent heating, it' necessary.

Comparative experiments, in which 1 molecule of pyroracemic acid wasbrought into reaction with 1 molecule, 1.3 molecules, 1.5 molecules and1.75 molecules of benzylidene-aniline, gave yields of 50%, 65%, 75% and80% of the theoretical yield of Q-phenylquinolinel-carboxylic acid. Thepossibility of obtaining yields of 75-80% and more when Workingaccording to the invention indicates undoubtedly an important additionto the art, particularly in view of the considerable value of the endproduct.

2. 88 parts by weight of a 50% aqueous solution of pyroracemic acid areadded to a boiling alcoholic solution of 155 parts by" weight ofbenzylidene-aniline and boiling under reflux is continued for a furtherthree hours. After the main quantity of the alcohol has been distilledoff the greater part Further investigations have shown that quitegenerally optimum yields are obtained in the producton ofquinoline-4-carboxylic acids substituted in the second position by. arylor alkyl radicals if the condensation product from an aromatic amine andaldehyde is employed in considerableexcess as compared withthefpyroraeemic acid or a substitution product of the pyroracemio acid,for example, in such a manner that more than 1.5 molecules, preferably,for example, about 1.5 to 2 molecules, of the condeusation product areemployed per 1 molecule of pyroracemic acid; The quantity ofcondensation product to be added over and above the limiting value of1.5 molecules naturally depends, from case to case, on the increase ofyield which can be achieved by the increase in the amount added.

Ewamples.

COOII The reaction probably takes place according to the equation:

of the phenylquinoline carboxylic acid may be recovered fromthe motherliquor by further concentration and crystallization or by solution ofthe evaporated residue in' ether or benzol under agitation with causticsoda solution.

3. 28.6 grins. of B-naphthylamine (2 molecules) and 21.2 grins. ofbenzaldehyde (2 molecules) are dissolved in 400 c. e. of 95% ing thereaction and subsequently on cooling the2-phcnyl-naphthoquinoline-4-carboxylic acid, diflicultly soluble inalcohol, separates out. Yield, 95100% of the theoretical (with referenceto the pyroracemie acid introduced). The product has the probableformula:

T IIOOO VO If only 1 molecule of B-naphthylamine and 1 molecule ofbenzaldehyde is added per 1 molecule of pyroracemic acid, a yield of 52%only of the theoretical is obtained.

4:. 22.5 grms. (1 molecule) of condensation product from p-toluidine andanisic aldehyde are dissolved in 150 c.c. of alcohol. 5.5 grms. of 80%pyroracemic acid (half a molecule) are added to the boiling solution andboiling. is effected for 2 to 3 hours under the reflux condenser.Q-p-methoxyphenyl-G- methyl-quinolinei-carboxylic acid forms with ayield of about three times the weight of the pyroracemic acid added. Theprodact has the formula:

COOH

If 1 molecule of condensation product from p-toluidine and anisicaldehyde is employed per 1 molecule of pyroracemic acid,

the yield only amounts to 1.5 times the weight of pyroracemic acid.

What I claim is 1. A process for the production ofquinolilielc-earboxylic acids aryl-substituted in the second position,which consists in cansnyl-quin )line-el-earboxylic acid, which consistsin causing 1 molecule of pyroraeemic acid to react, in the presence ofalcohol, with more than 1.5 molecules of benzylideneaniline.

4. A process for the production of 2-phenyl-quinoline-4-carboxylic acid,which consists in causing 1 molecule of pyroracemie acid to react, inthe presence of alcohol, with from 1.5 to 2 molecules ofbenzylidene-aniline.

5. A process for the production of 2-phenyl-quinoline-4-earbexylic acid,which consists in causing 1 molecule of pyroracemic acid to react, inthe presence of alcohol, with about 2 molecules of benzylidene-aniline.

In testimony whereof I affix my signature.

a ALFRED HAUSSLER.

